Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation
| Autor: | Shang Bin Yu, Yong Chen, Albert Cheung-Hoi Yu, Qian Rong Liu, Ju Mei Liu, Zhi Shi, Feng Pan, Xin Xin Xiong, Longyan Li, Ke-Jun Cheng, Xiao Qian Chen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Programmed cell death
Biophysics Biology Biochemistry p38 Mitogen-Activated Protein Kinases chemistry.chemical_compound Cell Line Tumor Cytotoxic T cell Humans Propidium iodide Molecular Biology Piperlongumine chemistry.chemical_classification Reactive oxygen species Cell Death JNK Mitogen-Activated Protein Kinases Dioxolanes Cell Biology nervous system diseases Enzyme Activation chemistry Apoptosis Cell culture Astrocytes Cancer cell Cancer research Drug Screening Assays Antitumor Glioblastoma Reactive Oxygen Species |
| Zdroj: | Biochemical and biophysical research communications. 437(1) |
| ISSN: | 1090-2104 |
| Popis: | Piperlongumine (PL), a natural alkaloid isolated from the long pepper, may have anti-cancer properties. It selectively targets and kills cancer cells but leaves normal cells intact. Here, we reported that PL selectively killed glioblastoma multiforme (GBM) cells via accumulating reactive oxygen species (ROS) to activate JNK and p38. PL at 20μM could induce severe cell death in three GBM cell lines (LN229, U87 and 8MG) but not astrocytes in cultures. PL elevated ROS prominently and reduced glutathione levels in LN229 and U87 cells. Antioxidant N-acetyl-L-cysteine (NAC) completely reversed PL-induced ROS accumulation and prevented cell death in LN229 and U87 cells. In LN229 and U87 cells, PL-treatment activated JNK and p38 but not Erk and Akt, in a dosage-dependent manner. These activations could be blocked by NAC pre-treatment. JNK and p38 specific inhibitors, SB203580 and SP600125 respectively, significantly blocked the cytotoxic effects of PL in LN229 and U87 cells. Our data first suggests that PL may have therapeutic potential for one of the most malignant and refractory tumors GBM. |
| Databáze: | OpenAIRE |
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